FAAH inhibition against pain, or perhaps just supplementing by palmitoylethanolamide?

Supplementing PEA or FAAH inhibition?

Palmitoylethanolamide is metabolized among others by FAAH. The more you can inhibit FAAH, the more PEA available. Sadly enougfh FAAH inhibitors are not so very specific and if one wants to boost endogenous palmitoylethanolamide, supplementing patients with the supplement PeaPure seems more logical.

Nevertheless, that is not patentable, and thus the search for patentable compounds able to inhibit FAAH and related enzymes continues.

FAAH inhibition and neuropathic pain

Tuan Trang from the University of Toronto Centre for the Study of Pain wrote a crisp article titled:

There are limited treatment options for neuropathic pain, a debilitating condition characterized by pain hypersensitivity. There is, however, growing interest in cannabinoids because CB1- and CB2- receptor agonists are analgesic in acute and chronic pain, and increases in endogenous cannabinoids are effective in ani- mal models of neuropathic pain (Bridges et al., 2001; Jayamanne et al., 2006).

This is not entirely correct, as PEA for instance is not a cannabinoid, it does not have any affinity to the classical Cannabinoid receptor.

The author refered to the spinal administration of URB597 also inhibited mechanically evoked responses of wide dynamic-range neurons and elevated endocannabinoid levels in the ipsilateral spinal cord of sham and SNL rats. He decribed the actions of URB597 which were blocked by pretreatment with AM-251, a CB1- receptor antagonist, and by naloxone, an opioid-receptor antagonist.

He concluded that the functional effects of URB597 are me- diated by CB1-receptors and involve interaction with the endogenous opioid system. The mechanism underlying such interaction is not known, but CB1-receptors are colocalized with 􏰀-opioid receptors in the spinal dorsal horn, suggesting a convergence of intracellular signaling between the two systems.